The mu opiate receptor (MOR) has been identified as the principal brain receptor site best correlated with the analgesic and euphoric properties of cocaine. Cellular and subcellular localization data are important to help to elucidate the functional properties of this important brain molecule. In this FY, studies of the distribution of the MOR protein in rat brain were substantially advanced. Light-microscopy revealed details of the distribution of MOR distribution in rat brain that included remarkable fiber distributions innervating the ventral tegmental area, and densely-immunoreactive perikarya, fibers and nerve terminals in the nucleus accumbens. Ultrastructural studies of the MOR revealed that most immunoreactivity was found in intracellular and plasma membrane localizations not readily associated with conventional synaptic specializations in spinal cord dorsal horn and in nucleus accumbens. Some MOR sites were postsynaptic to enkephalin-immunopositive neural elements, and some enkephalin-immunopositive elements contained apparent MOR Aautoreceptors. MOR regulation was also sought in inflammatory and other models. These studies substantially add to information on the detailed cellular localizations of these important sites for opiate analgesia and reward, and underscore the possibility that these receptors mediate primarily activities of opiate drugs and opioid peptides at sites away from synaptic specializations.